A compassion-based program to reduce psychological distress in medical students: A pilot randomized clinical trial.

OBJECTIVES: Physicians and medical students are subject to higher levels of psychological distress than the general population. These challenges have a negative impact in medical practice, leading to uncompassionate care. This pilot study aims to examine the feasibility of Compassion Cultivation Training (CCT) to reduce psychological distress and improve the well-being of medical students. We hypothesize that the CCT program, as compared to a waitlist control group, will reduce psychological distress (i.e., stress, anxiety, and depression) and burnout symptoms, while improving compassion, empathy, mindfulness, resilience, psychological well-being, and emotion-regulation strategies after the intervention. Furthermore, we hypothesize that these improvements will be maintained at a two-month follow-up. METHODS: Medical students were randomly assigned to an 8-week CCT or a Waitlist control group (WL). They completed self-report assessments at pre-intervention, post-intervention, and a 2-month follow-up. The outcomes measured were compassion, empathy, mindfulness, well-being, resilience, emotional regulation, psychological distress, burnout, and COVID-19 concern. Mixed-effects models and Reliable Change Index were computed. RESULTS: Compared with WL, CCT showed significant improvements in self-compassion, mindfulness, and emotion regulation, as well as a significant decrease in stress, anxiety, and emotional exhaustion component of burnout. Furthermore, some of these effects persisted at follow-up. No adverse effects of meditation practices were found. CONCLUSIONS: CCT enhanced compassion skills while reducing psychological distress in medical students, this being critical to preserving the mental health of physicians while promoting compassionate care for patients. The need for institutions to include this type of training is also discussed.

CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix.

Abnormal development of the ocular anterior segment may lead to a spectrum of clinical phenotypes ranging from primary congenital glaucoma (PCG) to variable anterior segment dysgenesis (ASD). The main objective of this study was to identify the genetic alterations underlying recessive congenital glaucoma with ASD (CG-ASD). Next-generation DNA sequencing identified rare biallelic CPAMD8 variants in four patients with CG-ASD and in one case with PCG. CPAMD8 is a gene of unknown function and recently associated with ASD. Bioinformatic and in vitro functional evaluation of the variants using quantitative reverse transcription PCR and minigene analysis supported a loss-of-function pathogenic mechanism. Optical and electron microscopy of the trabeculectomy specimen from one of the CG-ASD cases revealed an abnormal anterior chamber angle, with altered extracellular matrix, and apoptotic trabecular meshwork cells. The CPAMD8 protein was immunodetected in adult human ocular fluids and anterior segment tissues involved in glaucoma and ASD (i.e., aqueous humor, non-pigmented ciliary epithelium, and iris muscles), as well as in periocular mesenchyme-like cells of zebrafish embryos. CRISPR/Cas9 disruption of this gene in F0 zebrafish embryos (96 hpf) resulted in varying degrees of gross developmental abnormalities, including microphthalmia, pharyngeal maldevelopment, and pericardial and periocular edemas. Optical and electron microscopy examination of these embryos showed iridocorneal angle hypoplasia (characterized by altered iris stroma cells, reduced anterior chamber, and collagen disorganized corneal stroma extracellular matrix), recapitulating some patients' features. Our data support the notion that CPAMD8 loss-of-function underlies a spectrum of recessive CG-ASD phenotypes associated with extracellular matrix disorganization and provide new insights into the normal and disease roles of this gene.

Time course of bilateral microglial activation in a mouse model of laser-induced glaucoma.

Microglial activation is associated with glaucoma. In the model of unilateral laser-induced ocular hypertension (OHT), the time point at which the inflammatory process peaks remains unknown. Different time points (1, 3, 5, 8, and 15 d) were compared to analyze signs of microglial activation both in OHT and contralateral eyes. In both eyes, microglial activation was detected in all retinal layers at all time points analyzed, including: i) increase in the cell number in the outer segment photoreceptor layer and plexiform layers (only in OHT eyes) from 3 d onward; ii) increase in soma size from 1 d onward; iii) retraction of the processes from 1 d in OHT eyes and 3 d in contralateral eyes; iv) increase in the area of the retina occupied by Iba-1+ cells in the nerve fiber layer/ganglion cell layer from 1 d onward; v) increase in the number of vertical processes from 1 d in contralateral eyes and 3 d in OHT eyes. In OHT eyes at 24 h and 15 d, most Iba-1+ cells were P2RY12+ and were down-regulated at 3 and 5 d. In both eyes, microglial activation was stronger at 3 and 5 d (inflammation peaked in this model). These time points could be useful to identify factors implicated in the inflammatory process.

Caracterización clínica epidemiológica del cáncer de pulmón en pacientes atendidos de 2016 a 2017 / Epidemiological and clinical characterization of lung cancer in patients treated during 2016-2017

RESUMEN Introducción: el cáncer de pulmón se ha convertido a nivel mundial en un problema sanitario de primer orden. En Cuba, dentro de las neoplasias, este es el primero en mortalidad y el segundo en incidencia. Objetivo: caracterizar clínica y epidemiológicamente a pacientes con cáncer de pulmón atendidos en el Hospital Clínico Quirúrgico Docente "Dr. León Cuervo Rubio" de Pinar del Río. Métodos: se realizó una investigación descriptiva de corte transversal desde el primero de enero del 2016 hasta el 31 de diciembre del 2017, la muestra estuvo constituida por 83 pacientes con diagnóstico histológico de cáncer de pulmón. Resultados: predominó el grupo de edades entre 61 a 80 años y el sexo masculino con el 63,85 %. El factor de riesgo más frecuente fue el fumador activo con un 93,98 %, la presentación clínica que predominó fue la bronconeumónica en un 49,40 % de los pacientes, mientras la localización anatómica más frecuente fue el lóbulo superior derecho con un 44,53 %. La variedad cito-histología más frecuente fue el carcinoma epidermoide con un 37,35 %, en el momento del diagnóstico se encontraban en estadio III el 51,81 % de los pacientes. Conclusiones: el cáncer de pulmón resultó más frecuente en el sexo masculino y el grupo entre 61 a 80 años. Hubo mayor representación en pacientes fumadores. Existió correlación entre el efecto acumulativo del tabaquismo y las probabilidades de desarrollar cáncer en fumadores, en especial con los de mayor tiempo de consumo y los que consumen mayor número de paquetes al año.

ABSTRACT Introduction: lung cancer has become a major health problem worldwide. In Cuba, among the neoplasms, this is the first cause in mortality and the second in incidence. Objective: to characterize clinically and epidemiologically lung cancer patients treated at "Dr. León Cuervo Rubio" Clinical-Surgical-Teaching Hospital in Pinar del Río. Methods: a cross-sectional and descriptive research was carried out from January 1, 2016 to December 31, 2017. The sample consisted of 83 patients with histological diagnosis of lung cancer. Results: the age group between 61 and 80 years and male sex predominated (63,85 %). The most frequent risk factor was active smoking with 93,98 %; the clinical presentation was predominantly bronchopneumonia in 49,40 % of patients, while the most frequent anatomical location was the right upper lobe with 44,53 %. The most frequent cytohistological type was epidermoid carcinoma with 37,35 %, at the time of diagnosis 51,81 % of patients were in stage III. Conclusions: lung cancer was more frequent in men and into the group between 61 and 80 years. There was a higher representation of heavy smokers. A correlation between the cumulative effect of smoking and the probabilities of developing cancer in smokers was observed, especially in those with the longest addition and in those who smoke the greatest number of packs per year.

Bilateral early activation of retinal microglial cells in a mouse model of unilateral laser-induced experimental ocular hypertension.

The immune system plays an important role in glaucomatous neurodegeneration. Retinal microglial reactivation associated with ganglion cell loss could reportedly contribute to the glaucoma progression. Recently we have described signs of microglia activation both in contralateral and ocular hypertension (OHT) eyes involving all retinal layers 15 days after OHT laser induction in mice. However, no works available have analyzed the microglial activation at earliest time points after OHT induction (24 h) in this experimental model. Thus, we seek to describe and quantify signs of microglia activation and differences depending on the retinal layer, 24 h after unilateral laser-induced OHT. Two groups of adult Swiss mice were used: age-matched control (naïve) and lasered. In the lasered animals, OHT eyes as well as contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1 and MHC-II. We quantified the number of microglial cells in the photoreceptor layer (OS), outer plexiform layer (OPL), and inner plexiform layer (IPL); the number of microglial vertical processes connecting the OPL and OS; the area of the retina occupied by Iba-1+ cells (Iba1-RA) in the nerve fiber layer-ganglion cell layer (NFL-GCL), the total arbor area of microglial cells in the OPL and IPL and; Iba-1+ cell body area in the OPL, IPL and NFL-GCL. In contralateral and OHT eyes the morphological features of Iba-1+ cell activation were: migration, enlargement of the cell body, higher degree of branching and reorientation of the processes, radial disposition of the soma and processes toward adjacent microglial plexuses, and presence of amoeboid cells acting as macrophages. These signs were more pronounced in OHT eyes. Most of Iba-1+ cells did not express MHC-II; rather, only dendritic and rounded cells expressed it. In comparison with naïve eyes, in OHT eyes and contralateral eyes no significant differences were found in the microglial cell number; but there was a significant increase in Iba1-RA. The total arbor area of microglial cells was significantly decreased in: i) OHT eyes with respect contralateral eyes and naïve-eyes in IPL; ii) OHT eyes with respect to naïve eyes in OPL. The number of microglial vertical processes connecting the OPL and OS were significantly increased in contralateral eyes compared with naïve-eyes and OHT eyes. In OPL, IPL and NFL-GCL, the cell body area of Iba-1+ cells was significantly greater in OHT eyes than in naïve and contralateral eyes, and greater in contralateral eyes than in naïve eyes. A non-proliferative microglial reactivation was detected both in contralateral eyes and in OHT eyes in an early time after unilateral laser-induced OHT (24 h). This fast microglial activation, which involves the contralateral eye, could be mediated by the immune system.

The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma.

Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions. The retina is an extension of the brain and therefore the inflammatory response in the brain can occur in the retina. The brain and retina are affected in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and glaucoma. AD is an age-related neurodegeneration of the CNS characterized by neuronal and synaptic loss in the cerebral cortex, resulting in cognitive deficit and dementia. The extracellular deposits of beta-amyloid (Aß) and intraneuronal accumulations of hyperphosphorylated tau protein (pTau) are the hallmarks of this disease. These deposits are also found in the retina and optic nerve. PD is a neurodegenerative locomotor disorder with the progressive loss of dopaminergic neurons in the substantia nigra. This is accompanied by Lewy body inclusion composed of α-synuclein (α-syn) aggregates. PD also involves retinal dopaminergic cell degeneration. Glaucoma is a multifactorial neurodegenerative disease of the optic nerve, characterized by retinal ganglion cell loss. In this pathology, deposition of Aß, synuclein, and pTau has also been detected in retina. These neurodegenerative diseases share a common pathogenic mechanism, the neuroinflammation, in which microglia play an important role. Microglial activation has been reported in AD, PD, and glaucoma in relation to protein aggregates and degenerated neurons. The activated microglia can release pro-inflammatory cytokines which can aggravate and propagate neuroinflammation, thereby degenerating neurons and impairing brain as well as retinal function. The aim of the present review is to describe the contribution in retina to microglial-mediated neuroinflammation in AD, PD, and glaucomatous neurodegeneration.

Situs inversus del nervio óptico. A propósito de un caso / Situs inversus of the optic nerve. A case report

Introducción. El situs inversus del nervio óptico es una anomalía congénita caracterizada por la emergencia de los vasos de la retina en dirección nasal en lugar de temporal. Es causado por una anómala inserción del tallo óptico en la vesícula óptica que da lugar a la variación de disposición de la cabeza del nervio óptico. No es una condición aislada y suele aparecer junto con el síndrome del disco inclinado y en pacientes con miopía. Se caracteriza por la presencia de un cono de atrofia inferior, defectos en el campo visual temporal, defectos de refracción y ambliopía. Caso clínico. Mujer de 22 años, que acude a revisión oftalmológica por presentar fuertes cefaleas frontales acompañadas de halos y pérdida de nitidez en la visión. Tras un examen optométrico y oftalmológico se llega al juicio clínico de que padece un cuadro compatible con esta anomalía anatómica congénita. Conclusiones. El situs inversus del nervio óptico es una condición rara que puede aparecer aislada o acompañada de otras patologías. La aplicación de la campimetría y de nuevas técnicas diagnósticas, como la tomografía de coherencia óptica, facilita el diagnóstico diferencial de esta situación. No se conoce su prevalencia, pues no se encuentra en el registro de las enfermedades raras. Además, el escaso número de pacientes estudiados y la exigua bibliografía existente sobre esta anomalía no permiten conocer si los defectos causados progresan en el tiempo, por lo que sería importante realizar un seguimiento oftalmológico de los pacientes con situs inversus del nervio óptico (AU)

Introduction. Situs inversus of the optic nerve is a congenital anomaly characterised by the emergence of the vessels in the retina towards the nose rather than in a temporal direction. It is caused by an anomalous insertion of the optic stalks into the optic vesicle that gives rise to dysversion of the head of the optic nerve. It is not an isolated condition and usually appears jointly with tilted disc syndrome and in patients with myopia. It is characterised by the presence of inferior conus atrophy, deficiencies in the temporal visual field, refraction defects and ambliopy. Case report. A 22 years-old female who attended an ophthalmological examination due to severe frontal headaches accompanied by halos and loss of sharpness in her sight. From the results of the ophthalmetric and ophthalmological examination she was diagnosed as suffering from a condition consistent with this congenital anatomical anomaly. Conclusions. Situs inversus of the optic nerve is a rare condition that may appear in isolation or accompanied by other pathologies. Application of the visual field test and new diagnostic techniques, such as optical coherence tomography, facilitates the differential diagnosis of this situation. Its prevalence remains unknown, as it is not included in the register of rare diseases. Moreover, the scant number of patients studied and the scarce literature on this anomaly do not allow us to know whether the defects it causes develop over time. It would therefore be important to perform an ophthalmological follow-up of patients with situs inversus of the optic nerve (AU)

Goniodysgenesis variability and activity of CYP1B1 genotypes in primary congenital glaucoma.

Mutations in the CYP1B1 gene are currently the main known genetic cause of primary congenital glaucoma (PCG), a leading cause of blindness in children. Here, we analyze for the first time the CYP1B1 genotype activity and the microscopic and clinical phenotypes in human PCG. Surgical pieces from trabeculectomy from patients with PCG (n = 5) and sclerocorneal rims (n = 3) from cadaver donors were processed for transmission electron microscopy. Patients were classified into three groups depending on goniodysgenesis severity, which was influenced by CYP1B1 enzymatic activity. The main histological changes observed in the outflow pathway of patients with PCG and mutations in CYP1B1 were: i) underdeveloped collector channels and the Schlemm's canal; ii) abnormal insertion of the ciliary muscle; iii) death of the trabecular endothelial cells. Our findings could be useful in improving treatment strategy of PCG associated with CYP1B1 mutations.

Retinal Macroglial Responses in Health and Disease.

Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes and Müller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors. Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases. The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies.

Neuroprotective Effects of Low-Dose Statins in the Retinal Ultrastructure of Hypercholesterolemic Rabbits.

To evaluate the pleiotropic effects to statins, we analyze the qualitative and quantitative retinal changes in hypercholesterolemic rabbits after a low-dosage statin treatment. For this purpose, New Zealand rabbits were split into three groups: control (G0; n = 10), fed a standard diet; hypercholesterolemic (G1; n = 8), fed a 0.5% cholesterol-enriched diet for 8 months; and statins (G2; n = 8), fed a 0.5% cholesterol-enriched diet for 8 months, together with the administration of statin (pravastatin or fluvastatin sodium) at a dose of 2 mg / kg / day each diet. The retinas were analyzed by transmission electron microscopy and immunohistochemistry (glial fibrillary acidic protein). The retinal thickness of nuclear and plexiform layers were quantified in semi-thin sections. The results revealed that the low-statin-treated rabbits in comparison with the hypercholesterolemic group showed: i) a more preserved structure in all retinal layers; ii) a significant reduction in retinal thickness; iii) a decrease in cell death in the nuclear-and ganglion-cell layers; iv) a reduction of hydropic degeneration in the plexiform and nerve-fiber layers; v) a preservation of astrocytes and of the retinal area occupied by them; and vi) a better-preserved retinal vascular structure. Our findings indicate that low doses of statins can prevent retinal degeneration, acting on retinal macroglia, neurons and retinal vessels, despite that hypercholesterolemia remained unchanged. Thus, the pleiotropic effects of the statins may help safeguard the retinal ultrastructure.

Analysis of Retinal Peripapillary Segmentation in Early Alzheimer's Disease Patients.

Decreased thickness of the retinal nerve fiber layer (RNFL) may reflect retinal neuronal-ganglion cell death. A decrease in the RNFL has been demonstrated in Alzheimer's disease (AD) in addition to aging by optical coherence tomography (OCT). Twenty-three mild-AD patients and 28 age-matched control subjects with mean Mini-Mental State Examination 23.3 and 28.2, respectively, with no ocular disease or systemic disorders affecting vision, were considered for study. OCT peripapillary and macular segmentation thickness were examined in the right eye of each patient. Compared to controls, eyes of patients with mild-AD patients showed no statistical difference in peripapillary RNFL thickness (P > 0.05); however, sectors 2, 3, 4, 8, 9, and 11 of the papilla showed thinning, while in sectors 1, 5, 6, 7, and 10 there was thickening. Total macular volume and RNFL thickness of the fovea in all four inner quadrants and in the outer temporal quadrants proved to be significantly decreased (P < 0.01). Despite the fact that peripapillary RNFL thickness did not statistically differ in comparison to control eyes, the increase in peripapillary thickness in our mild-AD patients could correspond to an early neurodegeneration stage and may entail the existence of an inflammatory process that could lead to progressive peripapillary fiber damage.

Automatic Counting of Microglial Cells in Healthy and Glaucomatous Mouse Retinas.

Proliferation of microglial cells has been considered a sign of glial activation and a hallmark of ongoing neurodegenerative diseases. Microglia activation is analyzed in animal models of different eye diseases. Numerous retinal samples are required for each of these studies to obtain relevant data of statistical significance. Because manual quantification of microglial cells is time consuming, the aim of this study was develop an algorithm for automatic identification of retinal microglia. Two groups of adult male Swiss mice were used: age-matched controls (naïve, n = 6) and mice subjected to unilateral laser-induced ocular hypertension (lasered; n = 9). In the latter group, both hypertensive eyes and contralateral untreated retinas were analyzed. Retinal whole mounts were immunostained with anti Iba-1 for detecting microglial cell populations. A new algorithm was developed in MATLAB for microglial quantification; it enabled the quantification of microglial cells in the inner and outer plexiform layers and evaluates the area of the retina occupied by Iba-1+ microglia in the nerve fiber-ganglion cell layer. The automatic method was applied to a set of 6,000 images. To validate the algorithm, mouse retinas were evaluated both manually and computationally; the program correctly assessed the number of cells (Pearson correlation R = 0.94 and R = 0.98 for the inner and outer plexiform layers respectively). Statistically significant differences in glial cell number were found between naïve, lasered eyes and contralateral eyes (P<0.05, naïve versus contralateral eyes; P<0.001, naïve versus lasered eyes and contralateral versus lasered eyes). The algorithm developed is a reliable and fast tool that can evaluate the number of microglial cells in naïve mouse retinas and in retinas exhibiting proliferation. The implementation of this new automatic method can enable faster quantification of microglial cells in retinal pathologies.

Macro- and microglial responses in the fellow eyes contralateral to glaucomatous eyes.

Most studies employing experimental models of unilateral glaucoma have used the normotensive contralateral eye as the normal control. However, some studies have recently reported the activation of the retinal macroglia and microglia in the uninjured eye, suggesting that the eye contralateral to experimental glaucoma should not be used as a control. This review analyzes the studies describing the contralateral findings and discusses some of the routes through which the signals can reach the contralateral eye to initiate the glial reactivation.

Prevalencia de microalbuminuria en niños obesos e hipertensos y su relación con factores de riesgo cardiovascular / Prevalence of microalbumin in obese and hypertensive children and its relation with cardiovascular risk factors

Introducción: la microalbuminuria fue descrita por Keen y Chloverakis, quienes desarrollaron en 1963 un radio-inmuno-ensayo para detectar la eliminación urinaria de albúmina. Objetivo: identificar la prevalencia de microalbuminuria en niños obesos e hipertensos y su relación con otros factores de riesgo cardiovascular. Material y método: se realizó un estudio observacional, descriptivo, transversal de los educandos pertenecientes al semi-internado "Salvador González Delgado" de la ciudad de Pinar del Río, distribuidos en grupos escolares, entre enero y diciembre de 2012. Para el estudio las variables cualitativas se resumieron mediante frecuencias absolutas y relativas. Se calculó el intervalo de confianza para un 95%. Para detectar confusión o interacción se utilizó el análisis estratificado de Mantel y Haenszel y para la comparación de medias de variables con distribución normal, la prueba de diferencia de medias de la t de Student. Resultados: el 31,9% de las niñas eran obesas y los varones 32,6%. La microalbuminuria se presentó en el 11,5% de las niñas y 7,4% de los varones, todos los cuales eran obesos. Entre las niñas e l2,7% era hipertensa mientras el 3,7% varones. Con alteración de la circunferencia de la cintura 9.8% féminas y 11,7% varones. Conclusiones: se encontró altamente significativa la relación entre la obesidad y la microalbuminuria. La circunferencia de la cintura alterada se relacionaba significativamente con el incremento de los valores de la microalbuminuria. Hubo una asociación significativa entre la hipertensión arterial y microalbuminuria en ambos sexos, sin embargo; esta última variable fue considerada una variable confusora.

Introduction: microalbumin was described by Keen and Chloverakis, who developed in 1963 a radial-immune-essay for detecting urinary elimination of albumin. Objetive: to identify the prevalence of microalbumin in obese and hypertensive children and its relation with cardiovascular risk factors. Material and method: an observational, descriptive, cross-sectional study was performed with the students from Salvador González Delgado Primary School of Pinar del Río, distributed in academic groups, between January and December 2012. For the study, the qualitative variables were summarized by means of absolute and relative frequencies. The confidence interval was calculated for 95%. To detect confusion and interaction Mantel and Haenszel statistical analysis was used, while to compare variables measures with normal distribution, the Student’s T difference test of measures was used. Results: 31.9% of the girls and 32.6% of the males were obese. Microlabumin was present in 11.5% of the girls and 7.4% of the males, all of who were obese. Among the girls, 2.7% were hipertensive, while 3.7% were male. With alteration of the waist circunference of 9.8% of the girls and 11.7% of the males. Conclusions: it was found a highly significant relation between obesity and microalbumin. The altered waist circumference was highly related with the increase in microalbumin values. There was a significant association between hypertension and microalbumin in both sexes; however, this latter variable was considered as confusing variable.

Ophthalmologic Psychophysical Tests Support OCT Findings in Mild Alzheimer's Disease.

Purpose. To analyze in mild Alzheimer's disease (MAD) patients, GDS-4 (Reisberg Scale), whether or not some psychophysical tests (PTs) support OCT macular findings in the same group of MAD patients reported previously. Methods. Twenty-three MAD patients and 28 age-matched control subjects with mean Mini Mental State Examination of 23.3 and 28.2, respectively, with no ocular disease or systemic disorders affecting vision were included. Best-corrected visual acuity (VA), contrast sensitivity (CS) (3, 6, 12, and 18 cpds), color perception (CP), and perception digital test (PDT) were tested in one eye of each patient. Results. In comparison with the controls, MAD patients presented (i) a significant decrease in VA, PDT, and CS for all spatial frequencies analyzed, especially the higher ones, and (ii) a significant increase in unspecific errors on the blue axis (P < 0.05 in all instances). In MAD patients, a wide aROC curve was plotted in all PTs. Conclusions. In MAD, CS, VA, and the tritan axis in CP were impaired. The PTs with the greatest predictive value are the higher spatial frequencies in CS and tritan unspecific errors in CP. PT abnormalities are consistent with the structural findings reported in the same MAD patients using OCT.

Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology.

Most of the posterior segment diseases are chronic and multifactorial and require long-term intraocular medication. Conventional treatments of these pathologies consist of successive intraocular injections, which are associated with adverse effects. Successful therapy requires the development of new drug delivery systems able to release the active substance for a long term with a single administration. The present work involves the description of a new generation of microspheres based on poly(ester amide)s (PEA), which are novel polymers with improved biodegradability, processability and good thermal and mechanical properties. We report on the preparation of the PEA polymer, PEA microspheres (PEA Ms) and their characterization. PEA Ms (~15µm) were loaded with a lipophilic drug (dexamethasone) (181.0±2.4µg DX/mg Ms). The in vitro release profile of the drug showed a constant delivery for at least 90days. Based on the data from a performed in vitro release study, a kinetic ocular model to predict in vivo drug concentrations in a rabbit vitreous was built. According to the pharmacokinetic simulations, intravitreal injection of dexamethasone loaded PEA microspheres would provide release of the drug in rabbit eyes up to 3months. Cytotoxicity studies in macrophages and retinal pigment epithelial cells revealed a good in vitro tolerance of the microsystems. After sterilization, PEA Ms were administered in vivo by subtenon and intravitreal injections in male Sprague-Dawley rats and the location of the microspheres in rat eyes was monitored. We conclude that PEA Ms provide an alternative delivery system for controlling the delivery of drugs to the eye, allowing a novel generation of microsphere design.

Morphologic differences observed by scanning electron microscopy according to the reason for pseudophakic IOL explantation.

PURPOSE: To compare variations in surface morphology, as studied by scanning electron microscopy (SEM), of explanted intraocular lenses (IOLs) concerning the cause leading to the explantation surgery. METHODS: In this prospective multicenter study, explanted IOLs were analyzed by SEM and energy-dispersive X-ray spectroscopy. The IOLs were explanted in the centers of the research group from 2006 to 2012. The primary procedure was phacoemulsification in all cases. RESULTS: The study evaluated 40 IOLs. The main causes for explantation were IOL dislocation, refractive error, and IOL opacification. Those explanted due to dislocation demonstrated calcifications in 8 lenses (50%), salt precipitates in 6 cases (37.5%), and erythrocytes and fibrosis/fibroblasts in 2 cases (12.5%). In the refractive error cases, the SEM showed proteins in 5 cases (45.5%) and salt precipitates in 4 lenses (36.4%). In IOL opacification, the findings were calcifications in 2 of the 3 lenses (66.6%) and proteins in 2 lenses (66.6%). CONCLUSIONS: A marked variation in surface changes was observed by SEM. Findings did not correlate with cause for explantation. Scanning electron microscopy is a useful tool that provides exclusive information regarding the IOL biotolerance and its interactions with surrounding tissues.

Microglia in mouse retina contralateral to experimental glaucoma exhibit multiple signs of activation in all retinal layers.

BACKGROUND: Glaucomatous optic neuropathy, a leading cause of blindness, can progress despite control of intraocular pressure - currently the main risk factor and target for treatment. Glaucoma progression shares mechanisms with neurodegenerative disease, including microglia activation. In the present model of ocular hypertension (OHT), we have recently described morphological signs of retinal microglia activation and MHC-II upregulation in both the untreated contralateral eyes and OHT eyes. By using immunostaining, we sought to analyze and quantify additional signs of microglia activation and differences depending on the retinal layer. METHODS: Two groups of adult Swiss mice were used: age-matched control (naïve, n = 12), and lasered (n = 12). In the lasered animals, both OHT eyes and contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1, MHC-II, CD68, CD86, and Ym1. The Iba-1+ cell number in the plexiform layers (PL) and the photoreceptor outer segment (OS), Iba-1+ arbor area in the PL, and area of the retina occupied by Iba-1+ cells in the nerve fiber layer-ganglion cell layer (NFL-GCL) were quantified. RESULTS: The main findings in contralateral eyes and OHT eyes were: i) ameboid microglia in the NFL-GCL and OS; ii) the retraction of processes in all retinal layers; iii) a higher level of branching in PL and in the OS; iv) soma displacement to the nearest cell layers in the PL and OS; v) the reorientation of processes in the OS; vi) MHC-II upregulation in all retinal layers; vii) increased CD68 immunostaining; and viii) CD86 immunolabeling in ameboid cells. In comparison with the control group, a significant increase in the microglial number in the PL, OS, and in the area occupied by Iba-1+ cells in the NFL-GCL, and significant reduction of the arbor area in the PL. In addition, rounded Iba-1+ CD86+ cells in the NFL-GCL, OS and Ym1+ cells, and rod-like microglia in the NFL-GCL were restricted to OHT eyes. CONCLUSIONS: Several quantitative and qualitative signs of microglia activation are detected both in the contralateral and OHT eyes. Such activation extended beyond the GCL, involving all retinal layers. Differences between the two eyes could help to elucidate glaucoma pathophysiology.

Rod-like microglia are restricted to eyes with laser-induced ocular hypertension but absent from the microglial changes in the contralateral untreated eye.

In the mouse model of unilateral laser-induced ocular hypertension (OHT) the microglia in both the treated and the normotensive untreated contralateral eye have morphological signs of activation and up-regulation of MHC-II expression in comparison with naïve. In the brain, rod-like microglia align to less-injured neurons in an effort to limit damage. We investigate whether: i) microglial activation is secondary to laser injury or to a higher IOP and; ii) the presence of rod-like microglia is related to OHT. Three groups of mice were used: age-matched control (naïve, n=15); and two lasered: limbal (OHT, n=15); and non-draining portion of the sclera (scleral, n=3). In the lasered animals, treated eyes as well as contralateral eyes were analysed. Retinal whole-mounts were immunostained with antibodies against, Iba-1, NF-200, MHC-II, CD86, CD68 and Ym1. In the scleral group (normal ocular pressure) no microglial signs of activation were found. Similarly to naïve eyes, OHT-eyes and their contralateral eyes had ramified microglia in the nerve-fibre layer related to the blood vessel. However, only eyes with OHT had rod-like microglia that aligned end-to-end, coupling to form trains of multiple cells running parallel to axons in the retinal surface. Rod-like microglia were CD68+ and were related to retinal ganglion cells (RGCs) showing signs of degeneration (NF-200+RGCs). Although MHC-II expression was up-regulated in the microglia of the NFL both in OHT-eyes and their contralateral eyes, no expression of CD86 and Ym1 was detected in ramified or in rod-like microglia. After 15 days of unilateral lasering of the limbal and the non-draining portion of the sclera, activated microglia was restricted to OHT-eyes and their contralateral eyes. However, rod-like microglia were restricted to eyes with OHT and degenerated NF-200+RGCs and were absent from their contralateral eyes. Thus, rod-like microglia seem be related to the neurodegeneration associated with HTO.